Collagenases, enzymes capable of degrading native collagen, are critically important in mediating the remodeling of collagen in both normal and pathologic circumstances. An understanding of the regulatory mechanisms for colagenase expression in vitro should provide insight into the in vivo importance of these enzymes in cutaneous dieases. Thus, these studies collagenese and to examine the effects of potential physiologic modulators of collagenase expression, such as the endogenous gene product itself, steroid hormones and/or the products of cell-cell interactions. These studies will be correlated with those employing cell-free translation of collagenase to determine the nature of the primary collagenase gene product(s) and to determine if modulations in collagenase expression in intact cells are reflected by changes in translatable mRNA. These investigations of normal biosynthetic regulation will be used as a basis for defining the nature of the defect resulting in enhanced synthesis of an aberrant form of collagenase in recessive dystrophic epidermolysis bullosa. Here, both biosynthetic and preparative methods will be used to characterize the regulatory defect and the putatively mutant procollagenase(s) and to establish the therapeutic potential of certain pharmacologic agents. In addition, we shall examine the genetic specificty of any aberration in synthesis and/or structure of collagenase. The biologic importance of these studies is not only to define the normal regulatory mechanisms for collagen degradation but also to develop accurate in vitro markers and rational therapeutic modalities for a devasting genetic cutaneous disease.